The subject? Prenatal treatment of congenital adrenal hyperplasia (CAH), a rare inherited defect in hormone production that leads to an overproduction of male hormones in utero. CAH can cause deformity of the developing female genitalia (male genital development is unaffected), and can also lead to more “masculinized” behavior in affected girls and women. Though most are heterosexual, women with CAH are more likely to be lesbian or bisexual than the general population.

Other critics point out that very few affected girls really need the very aggressive genital surgery performed in the past, and that very high doses of prenatal steroids appear to increase the risk of serious consequences for treated children, including poor growth, learning disabilities, and even mental retardation. Such alarming reports have led many researchers in the United States and Europe to call for an end to the practice.

Still, Dr. Maria New, a pediatric endocrinologist in New York–by far the most prominent advocate of prenatal treatment–has declared the practice to be effective and “safe for mother and child.” Problem is, she and her colleagues haven’t been very diligent in following the babies they’ve treated over the last three decades, so the real risks of the prenatal steroid therapy aren’t yet completely known.

There’s much more detail in the post, and if you’re not feeling science-y enough to tackle that one, fear not. I’ll be back with lighter fare soon!

PS: Even if you’re not feeling science-y today, head to OBOS and donate money to that very worthy organization! Start racking up those 2013 tax deductions!

Ahem… I’ve just been told that Science & Sensibility is having some spam problems, so apparently my post went up and came down quickly. Should be up again soon. In the meantime here’s the post (below). Check in at Science & Sensibility later to follow any comments that surface, or to further sabotage the site, as you see fit.

When I first learned some years ago that cesarean section was associated with an increased risk of childhood asthma and eczema, I eagerly awaited the rest of the story. What could the link possibly be? Epidurals? Anesthetics? Antibiotics? Something strange and exotic was afoot, I was certain.

Imagine my surprise, then, when a growing body of evidence pointed to an unexpected source: the newborn gastrointestinal tract and the microorganisms that live there.

How might intestinal bacteria play such a major role in the health and well-being of newborns and children? The answer lies in an ancient, mutually beneficial relationship, one that modern birth technology has dramatically altered.

* * *

Some friendly faces…

“Microbiota” is the term used to describe the community of microorganisms—bacteria, viruses, and fungi—that normally live in or on a given organ in the body. There’s a unique microbiota that inhabits the mouth, for example, another that lives on the skin, and still another that populates the intestine, or gut. Given an intestinal surface area of about 2,700 square feet—more or less the size of a tennis court—the microbiota inhabiting the gut is the largest and most diverse in the body.

How large and diverse? The gut microbiota contains roughly one quadrillion cells—at least ten times as many cells as does the human body itself. More than 1,000 bacterial species having been identified to date, with unknown numbers yet to be discovered.

How do all those bacteria get there? The fetal intestine, in the absence of congenital infection, is sterile in utero. The bacteria that come to colonize the bowel are acquired during birth and shortly afterwards, a process that is very much influenced by how a baby is born.

The gut microbiota and mode of delivery

In vaginally-born babies the colonizing bacteria originate primarily in the maternal birth canal and rectum. Once swallowed by the newborn during birth, these bacteria pass through the stomach and upper intestine and colonize the lower intestine, a complicated initial process that takes about a week.

Infants born by cesarean section—particularly cesareans performed before labor begins—don’t encounter the bacteria of the birth canal and maternal rectum. (If a cesarean is performed during labor the infant may be exposed to these bacteria, but to a lesser degree than in vaginal birth.) Instead, bacteria from the skin and hospital environment quickly populate the bowel. As a result, the bacteria inhabiting the lower intestine following a cesarean—the gut microbiota—can differ significantly from those found in the vaginally-born baby.

Whatever the mode of delivery, a core gut microbiota is well established within a few weeks of life and persists largely intact into adulthood. A less stable peripheral microbiota—one that is more sensitive to changes in diet and environmental factors, like antibiotics—is created as well. Between one and two years of age, when weaning from breast milk typically leads to a diet lower in fat and higher in carbohydrates, the gut microbiota takes on its final, mature profile.

Development of the newborn immune system

The dramatic first steps in immune system development take place at the same time the core microbiota is being formed, and the gut bacteria play a key role in that process.

In the hours and days following birth, the newly-arrived bacteria of the gut microbiota stimulate the newborn’s production of white blood

A t-lymphocyte

cells and other immune system components, as well as antibodies directed at unwelcome, disease-causing microorganisms. The bacteria of the microbiota also “teach” the newborn’s immune system to tolerate their own advantageous presence—to differentiate bacterial friend from foe, in other words.

In a cesarean birth the fledgling immune system is confronted with unfamiliar, often hostile bacteria—including Clostridium difficile, a particularly troublesome hospital-acquired bug. In addition, the healthy probiotic bacteria associated with vaginal birth that the newborn’s immune system expects to see arrive later and in lower numbers. These changes in the composition of the normal gut microbiota occur during a critical time in immune system development.

The cesarean-asthma theory (in a nutshell)

Here’s how cesareans and asthma are likely connected:

Humans evolved right along with the gut microbiota normally acquired during vaginal birth. When the composition of that microbiota is imbalanced, or unusual germs like Clostridium difficile appear, the immune system doesn’t like it. A low-grade, long-lasting inflammatory response directed at these intruders begins at birth, leading to a kind of “leakiness” of the intestinal lining. Proteins and carbohydrates that normally would not be absorbed from the intestinal contents—including large food molecules—make their way into the infant’s bloodstream.

To make a very long story short, that inflammation and the abnormal digestion and absorption of food that results appears to increase the risk of asthma and eczema—and diabetes, obesity, and other chronic illnesses—later in life.

* * *

Normalizing the post-cesarean gut microbiota

Reducing the cesarean rate is an obvious best practice in promoting a healthy gut microbiota. But there will always be a need for cesarean section, and so researchers are now beginning to focus on “normalization” of the gut microbiota of cesarean-born babies. Although there are as yet no proven therapies, here are some possibilities:

Probiotics. Though administering healthful probiotic bacteria to correct an imbalanced microbiota makes intuitive sense, studies to date have been disappointing. However, research into “good” bacteria and how they become established in the intestine is active and ongoing.

Direct transfer of maternal secretions. Placing maternal vaginal and rectal material into the newborn’s mouth has been proposed—more or less mimicking natural colonization—but to date there are no published studies to support the practice.

Fecal transplantation. Direct transfer of fecal material from healthy adults into the gastrointestinal tract of people suffering from Clostridium difficile infections has shown promise. Using healthy parents as “donors” for their babies has been proposed, but applying such technology to otherwise healthy newborns is highly impractical at present, to say the least.

Conclusion

A cesarean section doesn’t automatically doom a child to a lifetime of asthma or eczema, just as a vaginal birth isn’t an absolute guarantee of perfect health. But cesarean birth, by altering normal gut microbiota development, does appear to moderately increase the risk of these and other chronic health conditions. A woman who has the option of choosing her mode of delivery should consider this along with the many other factors she must weigh in deciding how her baby will be born.

How do babies decide what to concentrate on as they learn the ways of the world? And how do they keep from being overwhelmed by a world in which everything is new? Surprisingly (or maybe not), they act a lot like adults.

Writing in the journal PLoS ONE, Celeste Kidd and colleagues at the University of Rochester describe how babies learn: they use a “principled inferential process” and “appear to allocate their attention in order to maintain an intermediate level of complexity.”

Say what?

Fortunately Kidd saves the day by naming the process “the Goldilocks Effect.” (Quick refresher: Goldilocks stumbles into the bears’ cottage, finds their porridge to be either too hot or too cold, whines about her porridge-fate until she finally discovers a warm-ish bowl that’s “just right.” She eats it, settles into a “just right” bed, and goes to sleep. When the bears return they do not eat her, for reasons I’ve never quite understood.)

Kidd found that babies tend to spend most of their visual attention on things that are neither too simple nor too complicated. That is, they are attracted to “just right” complexity–enough to stimulate their brains, but not so dull as to put them to sleep, or so complex as to fry their little noggins.

This study confirms what many parents have long known: babies will seek out the level of stimulation in their environment that is appropriate to their learning needs. Bombarding them with extra, too-complex stimulation doesn’t accomplish much, other than to overwhelm them.

Watch a baby and you’ll know how much stimulation is too much. They simply look away when they’ve had enough. Kind of like me in my college calculus class…

Here’s a kind of counterpoint article, also from The Atlantic, to the one by Alice Dreger M.D. on low-intervention birth in my previous post. The author, Adam Wolfberg M.D., is an obstetrician at Tufts University who specializes in high risk pregnancies. Right from the article’s first sentence he’s pretty up front about where he thinks births should happen:

“I believe babies ought to be born in a hospital.”

That belief seems to be based on personal experience (I say “seems,” because the only case presented is of a couple who wanted a home birth, ran into trouble that led to transfer, and then were “annoyed” to have had a healthy baby in the hospital) and backed up by a reference to the study by J.R. Wax that purported to show a three-fold increase in infant mortality for babies born at home.

This essay actually offers unintended support to Dr. Dreger’s claim that physicians sometimes confuse science with technology. The Wax study has been heavily criticized for presenting a distorted picture of home birth safety (details here). Dr. Wolfberg ignores much research to the contrary in picking that particular study as evidence of the dangers of out-of-hospital birth, and his use of a badly flawed study to support hospital birth for all women is exactly the kind of thing Dr. Dreger decries.

As I said in my last post, I’ve been on both sides of this debate. Childbirth is sometimes a scary thing, and it doesn’t always end happily. I’ve seen the kind of birth disasters that make an aggressive approach to childbirth so attractive to physicians, and I’ve also taken care of babies harmed by that style of practice.

The trick is to find a safe balance of nature and technology for each mother and baby. That’s an elusive goal in the increasingly polarized world of American maternity care.

My career as a pediatrician attending births has been one long tale of learning a lot of stuff and then unlearning quite a bit of it. When I started in the late 1970s we went after even mildly distressed newborns like a medical SWAT team, with laryngoscopes, oxygen masks and umbilical catheters flying, snatching our pint-sized patients from the jaws of…what, exactly? In retrospect, a lot of them would have been just fine without us. Maybe even better off. (And just to be clear, a lot of them really needed the help, too…)

Things have changed remarkably since then. More and more studies support the wisdom of a patient, mother-centered approach to childbirth, though you wouldn’t know it from current epidural, induction and cesarean rates. Some of the refusal to accept what the research clearly tells us has to do with the way new doctors are often still taught to view childbirth: as a dangerous process in need of strict control. From the article:

“Many medical students, like most American patients, confuse science and technology. They think that what it means to be a scientific doctor is to bring to bear the maximum amount of technology on any given patient. And this makes them dangerous. In fact, if you look at scientific studies of birth, you find over and over again that many technological interventions increase risk to the mother and child rather than decreasing it.”

Add in the fact that you’re frequently scared to death as a med student and find technology a comfortable/comforting suit of armor to wear, and it’s not surprising that young doctors often live in fear of normal childbirth. I know…I was there. It only takes one bad outcome to make an aggressive approach look attractive, particularly when that’s the medical culture in which you’re being educated.

Dreger’s article is all the more interesting because she’s a professor of clinical medical humanities and bioethics at Northwestern University’s Feinberg School of Medicine, and her husband is an academic internist–not exactly the stereotype (e.g., the “woman who wears long cotton skirts, braids her hair, eats only organic vegan food, does yoga, and maybe drives a VW microbus,” as Dreger puts it) associated with midwifery and low-intervention births. But when Dreger and her husband did an extensive review of the scientific childbirth literature in 2000 and found that it supported just that–a low-intervention approach–they put what they learned into practice with the birth of their own child.

There’s a place for technology in childbirth, certainly, but most pregnancies don’t need nearly as much of it as they get in the U.S. these days.

Okay, now for a bit more detail about Vitamin D. In this post we’ll look at where it comes from, and how we get it to where it’s needed in the body.

1) Vitamin D metabolism

There are actually two forms of vitamin D: vitamin D2, which is synthesized by plants, and vitamin D3 (cholecalciferol), which is synthesized by mammals, including us. This review will focus on D3, since that’s the most important form for humans.

There are two ways that humans get their daily vitamin D: sunshine (the most effective way) and diet.

Not exactly true...

First let’s clear up a common vitamin D misconception. We do not get vitamin D directly from the sun–that is, there are no tiny “Ds” raining down on us while we sunbathe by the pool. Rather, sunlight acts on a cholesterol-based vitamin D precursor our bodies make and converts that to previtamin D in the skin. Previtamin D is then converted to vitamin D3 by the heat of the skin.

That’s just the beginning…

Once it leaves the skin, vitamin D3 jumps on board a specialized protein that transports it to the liver, where it’s converted to 25-hydroxyvitamin D (25-OH-D). From there 25-OH-D surfs to the kidneys on another specialized protein where, through the mysteries of biochemistry, it transforms itself into 1,25-dihydroxyvitamin D (1,25-OH2-D), the most biologically active form of vitamin D. Then it’s off to the tissues of the body to work some magic.*

We can also get vitamin D from what we eat, though D isn’t distributed very well in natural foods. Vitamin D-rich foods include oily fish like salmon and swordfish, and egg yolks, butter and liver (Liver!! My Gram Sloan, a big chicken liver fan, was right…). Vitamin D is added to milk nowadays, of course, but even so, unless you’re a traditional Eskimo–eating a lot of fish, seal and whale blubber–it’s unlikely that your daily diet provides more than half of your vitamin D needs.

2) Sunshine: How much is enough?

Many factors go into determining how much sun exposure we require to ensure a healthy level of vitamin D in the bloodstream. Time of year, latitude, skin pigmentation, weather, air pollution, clothing and sunscreen all play a role. Basically, a fair-skinned, sunscreen-free person getting 10-15 minutes of total body exposure during the summer months will produce about 10,000-25,000 international units (IU) of vitamin D in 24 hours. So a Celtic-skinned person (such as myself) living in a nudist colony on the equator (not gonna happen) would do just fine, vitamin D-wise, from sunshine alone…until the skin cancer gets him, that is.

But all those other factors, from clothing to clouds, literally get in the way. Take the simple factor of skin pigmentation: it can take 5 to 10 times more sunlight for a dark-skinned individual than a light-skinned one to produce the same amount of vitamin D. Consider the plight of, say, a Nigerian-born child living in

On the lookout for vitamin D...

Canada. Between the short northern winter days, cold-weather clothes and dark skin, the chances of getting enough vitamin D from sunshine are pretty remote.

And that’s true of just about everyone in the United States today, too, regardless of skin pigmentation. In a 1989 study on indoor air quality, the Environmental Protection Agency estimated that the average American spends 93% of his or her time indoors. Today, with computers, electronic games, and 600 TV channels to choose from, that sun-less percentage has likely increased, to the detriment of our vitamin D stores.

So, most of us are not getting nearly enough vitamin D from sunshine or diet. What potential impact does that have on our health?

Stay tuned…

* * *

*(Vitamin D metabolism, which involves skin, liver, kidneys, bowel, bones, sunlight, diet, heat, several specialized proteins and dozens of specific chemical reactions–and which can be disrupted by things like rainy weather, or how often you wear a hat outdoors–is not a good argument for intelligent design.)